A renal clearable fluorogenic probe for in vivo ß-galactosidase activity detection during aging and senolysis

Fecha de publicación:

Autores de CIPF

  • Beatriz Lozano Torres

    Autor

  • Irene Galiana Guillem

    Autor

  • Juan Francisco Blandez Barradas

    Autor

  • Ramón Martínez Mañez

    Autor

Participantes ajenos a CIPF

  • Rojas-Vázquez, S
  • García-Fernández, A
  • Perez-Villalba, A
  • Martí-Rodrigo, P
  • Palop, MJ
  • Domínguez, M
  • Sancenón, F
  • Fariñas, I

Grupos de Investigación

Abstract

Accumulation of senescent cells with age leads to tissue dysfunction and related diseases. Their detection in vivo still constitutes a challenge in aging research. We describe the generation of a fluorogenic probe (sulfonic-Cy7Gal) based on a galactose derivative, to serve as substrate for beta-galactosidase, conjugated to a Cy7 fluorophore modified with sulfonic groups to enhance its ability to diffuse. When administered to male or female mice, beta-galactosidase cleaves the O-glycosidic bond, releasing the fluorophore that is ultimately excreted by the kidneys and can be measured in urine. The intensity of the recovered fluorophore reliably reflects an experimentally controlled load of cellular senescence and correlates with age-associated anxiety during aging and senolytic treatment. Interestingly, our findings with the probe indicate that the effects of senolysis are temporary if the treatment is discontinued. Our strategy may serve as a basis for developing fluorogenic platforms designed for easy longitudinal monitoring of enzymatic activities in biofluids. In vivo detection of cell senescence remains a challenge in aging research. This work introduces a novel fluorogenic probe for beta-Gal activity that is excreted in urine, providing a simple diagnosis method to estimate the systemic load of senescent cells during aging and senolytic interventions.

Datos de la publicación

ISSN/ISSNe:
2041-1723, 2041-1723

Nature Communications  NATURE PUBLISHING GROUP

Tipo:
Article
Páginas:
775-775
PubMed:
38278798

Citas Recibidas en Web of Science: 19

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